Objective: To investigate the therapeutic effect of secukinumab combined with halometasone cream on patients with moderate to severe plaque psoriasis, and the impact on the severity of skin lesions and inflammatory factors. Methods: A total of 60 patients with moderate to severe plaque psoriasis who were admitted to Xinfeng County People"s Hospital from June 2023 to December 2024 were selected. They were assigned to the treatment group (30 cases treated with secukinumab combined with halometasone cream) and the control group (30 cases treated with halometasone cream combined with Avicenna capsules) according to the random number table method. Comparisons were made between groups on clinical efficacy, severity of skin lesions [Psoriasis Area and Severity Index (PASI) and body surface area (BSA)] and inflammatory factors [interleukin-17A (IL-17A), interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α)]. Results: The total clinical effective rate was 96.67% (29/30) in the treatment group and 73.33% (22/30) in the control group, and the former was higher (P<0.05). After treatment, both groups showed reductions in PASI and BSA scores, IL-17A, IFN-γ and TNF-α levels. Moreover, the reductions were greater in the treatment group (P<0.05). Conclusion: Secukinumab combined with halometasone cream is markedly effective in treating moderate to severe plaque psoriasis, which can significantly alleviate skin lesions and lower the levels of inflammatory factors in patients.